title: A hyperlipidemic rabbit model provides new insights into pulmonary zinc exposure effects on cardiovascular health.
abstract: This study ascertains the effects of zinc, a major component of particulate matter, on pulmonary and systemic endpoints using hyperlipidemic rabbits to model diet-induced human atherosclerosis. New Zealand White rabbits were fed a normal or cholesterol-enriched diet and then were intratracheally instilled 1x/week for 4 weeks with saline or 16 microg/kg of zinc, equal parts sulfate and oxide. Physiologic responses, blood after each exposure, and terminal bronchoalveolar lavage (BAL) were assessed. Rabbits fed a cholesterol-rich diet developed hyperlipidemia and had consistently higher circulating leukocyte counts than rabbits fed normal chow. Within minutes after zinc instillation, saturation of peripheral oxygen was decreased in hyperlipidemic rabbits and heart rate was increased in hyperlipidemic rabbits with total serum cholesterol levels greater than 200 mg/dl. Total circulating leukocytes levels were increased 24 h after the first zinc instillation, but upon repeated exposures this effect was attenuated. After repeated zinc exposures, BAL fluid (BALF) N-acetylglucosaminidase activity was increased regardless of hyperlipidemic state. Hyperlipidemic rabbits had an increase in BALF-oxidized glutathione and a decrease in serum nitrite. The study elucidates mechanisms by which the zinc metal component of PM drives cardiovascular health effects, as well as the possible susceptibility induced by hyperlipidemia. Furthermore, the study exemplifies the benefits of monitoring circulatory physiology during exposure as well as after exposure.
authors.affiliation: Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. lagier.adriana@epa.gov
authors.forename: Adriana J
authors.initials: AJ
authors.lastname: LaGier
authors.forename: Nick D
authors.initials: ND
authors.lastname: Manzo
authors.forename: Alex P
authors.initials: AP
authors.lastname: Carll
authors.forename: Richard H
authors.initials: RH
authors.lastname: Jaskot
authors.forename: Ralph
authors.initials: R
authors.lastname: Slade
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Winsett
authors.forename: Aimen K
authors.initials: AK
authors.lastname: Farraj
authors.forename: Janice A
authors.initials: JA
authors.lastname: Dye
mesh_terms: D000118:Acetylglucosaminidase / Q000032:analysis; D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019803:Glutathione Disulfide / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism*; D019570:Inhalation Exposure; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009573:Nitrites / Q000097:blood; D052638:Particulate Matter / Q000633:toxicity*; D011817:Rabbits; D015034:Zinc Oxide / Q000633:toxicity*; D019287:Zinc Sulfate / Q000633:toxicity*
chemical_list: D009573:Nitrites; D052638:Particulate Matter; D019287:Zinc Sulfate; D002784:Cholesterol; D000118:Acetylglucosaminidase; D015034:Zinc Oxide; D019803:Glutathione Disulfide